High incidence of outcome switching observed in follow-up publications of randomized controlled trials: Meta-research study

Objectives: To determine the incidence of outcome switching in follow-up publications of randomized controlled trials. Outcome switching leads to bias where treatment benefits are more likely to be overestimated or based on chance. Study design and setting: Meta-research study including all follow-up publications 2014-2018 in the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, and the British Medical Journal. Two independent reviewers compared the primary outcomes of follow-up publications with the original RCT publication and the trial protocol. Results: Seventy-eight follow-up publications were identified. Thirty-one (40%) used different primary outcomes in the follow-up publication compared with the original RCT. In seventeen (55%) of these the outcome switch was neither pre-specified nor explained in the journal publication. The incidence of outcome switching in follow-up studies rose to 70% when preceded by outcome switching in the corresponding initial RCT (P< 0.001). Conclusion: In this study, outcome switching occurred in 40% of follow-up publications of previously published RCTs. The majority is neither pre-specified nor explained.